Research in our lab focuses on developing new treatments for hyperammonemia and identifying blood biomarkers of brain injury from hyperammonemia. We discovered that AMP-activated protein kinase (AMPK) signaling regulates abundance of urea cycle enzymes in response to dietary protein intake; this makes AMPK signaling pathway an attractive target for therapies aimed at increasing abundance of urea cycle enzymes and capacity to convert ammonia into urea in patients with partial urea cycle disorders.
Our lab is also working on developing new treatments for hyperammonemia that focus on preventing irreversible brain injury by high ammonia concentrations. To discover and develop such treatments, we screened over 10,000 chemicals for their ability to protect zebrafish from ammonia toxicity; 31 of these compounds prolonged the survival of fish exposed to high ammonia. However, evaluation of these candidate drugs in both preclinical and clinical settings will require validated biomarkers for monitoring brain injury from hyperammonemia. We are currently evaluating use of S100B, neuron-specific enolase (NSE), and ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) as blood biomarkers of brain injury from hyperammonemia.